9-4572480-T-C

Position:

• chr9-4572480-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004170.6(SLC1A1):​c.767+92T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,107,596 control chromosomes in the GnomAD database, including 110,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17610 hom., cov: 33)
  • Exomes 𝑓: 0.43 (93258 hom.)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0280

Genes affected

SLC1A1 (HGNC:10939): (solute carrier family 1 member 1) This gene encodes a member of the high-affinity glutamate transporters that play an essential role in transporting glutamate across plasma membranes. In brain, these transporters are crucial in terminating the postsynaptic action of the neurotransmitter glutamate, and in maintaining extracellular glutamate concentrations below neurotoxic levels. This transporter also transports aspartate, and mutations in this gene are thought to cause dicarboxylicamino aciduria, also known as glutamate-aspartate transport defect. [provided by RefSeq, Mar 2010]

SPATA6L (HGNC:25472): (spermatogenesis associated 6 like) Predicted to enable myosin light chain binding activity. Predicted to be involved in spermatogenesis. Predicted to be located in sperm connecting piece. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-4572480-T-C is Benign according to our data. Variant chr9-4572480-T-C is described in ClinVar as [Benign]. Clinvar id is 1266422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.767+92T>C		intron_variant		ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.767+92T>C		intron_variant		1	NM_004170.6	ENSP00000262352.3
SLC1A1	ENST00000422398.1	c.53+92T>C		intron_variant		4		ENSP00000414620.1
SPATA6L	ENST00000485616.5	n.*782-18092A>G		intron_variant		2		ENSP00000420003.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71746 AN: 151974 Hom.: 17594 Cov.: 33

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.491

GnomAD4 exome AF: 0.434 AC: 414621 AN: 955502 Hom.: 93258 AF XY: 0.437 AC XY: 217013 AN XY: 496588

Gnomad4 AFR exome AF: 0.595

Gnomad4 AMR exome AF: 0.445

Gnomad4 ASJ exome AF: 0.560

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.479

Gnomad4 FIN exome AF: 0.334

Gnomad4 NFE exome AF: 0.432

Gnomad4 OTH exome AF: 0.457

GnomAD4 genome AF: 0.472 AC: 71809 AN: 152094 Hom.: 17610 Cov.: 33 AF XY: 0.468 AC XY: 34768 AN XY: 74364

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.492

Alfa AF: 0.447 Hom.: 20186

Bravo AF: 0.487

Asia WGS AF: 0.401 AC: 1392 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.69
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3780412; hg19: chr9-4572480; COSMIC: COSV52059352;